Development Of ABEEMσπ Fluctuating Charge Polarizable Force Field For Oxidized Purine Base Pairs

Hydrogen-bonding and stacking interactions play a unique role for structure and replicationof DNA. The integrity of the genetic information is constantly threatened by oxidizing agents.Oxidized bases have all been linked to different types of cancers. Taking high level quantumchemistry methods as benchmark, we developed the ABEEMσπ fluctuating charge force fieldfor base pairs containing oxidized purine, to study the structures and properties. We havedone a great deal of quantum chemistry methods, ABEEMσπ and other force fieldcalculations for investigation, testing and calibration. The main results are as follows:1. Choosing the proper quantum chemical methods, and doing the corresponding calculationsand analysis.B3LYP/6-31+G*level was choose among30quantum chemical methods to optimizedthe strutures and calculated the dipole moment by comparing with experimental date. Thecharge were calculated at HF/STO-3G level. The energies were determined atMP2/aug-cc-pVDZ level with BSSE corrections.2. Investigate of the flat structure of oxidized base pairs.ABEEMσπ force field and quantum chemistry methods obtaine the same conclution thatthe angle formed by two base planes is buckled in the oxidized base pairs, and36%ofbuckled angles of oxidized guanines are larger than5.0°, and79%of buckled angles ofoxidized adenine are larger than5.0°. Hydrogen bonding strength are increased by stackinginteraction.3. Investigation on the H-bonding and stacking interactions.Comparing the results of quantum chemistry method with those of ABEEMσπ, the linearcorrelation coefficients of the charges, dipole moments and interaction energies are0.99,0.96and0.96, respectively; The RMSD of H-bond lengths and H-bond angles in oxidized purineare0.031and1.8°, respectively. ABEEMσπ force filed gives reasonable geometries ofH-bonds compared with the quantum chemistry method for stacking interactions.4. Forcaste the mutation path induced by oxidized bases.In the DNA double helix, the mutations of ATâ†'CG, ATâ†'GC would happen induced byguanine, and the mutations of ATâ†'GC, ATâ†'TA or ATâ†'CG would happen induced byoxidized adenine in terms of binding energies. Meanwhile, the active centers of nucleophilicor electrophilic reaction transfer during ATâ†'GC, ATâ†'TA and ATâ†'CG mutations. The results indicate that the performance of the ABEEMσπ force field which is used tobase pairs of oxidized purine is generally better than that of the common force fields, and itsaccuracy can compare with that of the quantum chemistry method method. These studiessupply a solid basis for further investigations of dynamic behavior of DNA fragmentsincluding oxidized purine by the ABEEMσπ fluctuating charge force field.